1. Field of the Invention
The present invention relates to a non-invasive subject-information imaging method and apparatus for imaging living body anatomical, functional, and/or metabolic information of a subject to be examined by acquiring acoustic signals generated on the basis of the energy of light radiated into the subject and, more particularly, to a method and apparatus which acquire and superimpose two acoustic images, one generated from the energy of light radiated into a subject to be examined and the other is an ultrasound echo image generated from ultrasonic waves directed into the subject, and allow an operator to know the distribution of substance concentrations with respect to morphological features in the subject's tissue by superimposing the two images.
2. Description of the Related Art
A subject-information measuring method of measuring the concentration of a substance component contained in a body fluid such as blood or cell fluid in the subject or living body tissue has been performed in healthcare, determination on a therapeutic effect, and the like. In performing component analysis on a body fluid to measure the concentration of each component, the body fluid must be extracted from the subject by blood collection. This method therefore damages the skin of the subject, causing much pain to the subject. This also introduces the possibility of biohazard contamination to the subject and the operator.
With regard to such a conventional problem, a number of patents and journal articles describe non-invasive methods of acquiring information about analyte concentration in the tissue of human subjects. One of the methods is “photoacoustic spectroscopy”. In the photoacoustic spectroscopy, the concentration of a specific substance, such as glucose or hemoglobin, contained in the blood of a subject is quantitatively measured by detecting the acoustic waves that are generated when the subject is irradiated with visible light, infrared light, or intermediate infrared light having a predetermined wavelength, and the specific substance absorbs the energy of the irradiated light. With regard to this, U.S. Pat. No. 5,348,002, EP9838904A1, EP0215776A1 describe methods for the non-invasive determination of substances in human tissue using photoacoustic measurements. The light may be visible light, infrared light, or intermediate infrared light.
In addition to glucose and hemoglobin described above, cholesterol, natural fat, bilirubin, collagen, and the like can be used as substances as targets for non-invasive subject-information measurement. Diagnosis of cutaneous cancer or breast cancer by the photoacoustic spectroscopy has recently proven its clinical usefulness. The photoacoustic spectroscopy uses the wavelength of light at which an optimal substance selected from these substances exhibits the highest absorption. In addition, it is increasingly expected that an image diagnosis method be invented, which provides a two-dimensional image representing the concentration distribution of these substance.
In a conventional non-invasive method of measuring glucose, the skin of the subject is irradiated with near-infrared light beams of different wavelengths. The glucose concentration is measured by arithmetically processing the acoustic waves obtained (see, for example, Jpn. Pat. Appln. KOKOKU Publication Nos. 3-47099 and 5-58735).
The conventional photoacoustic spectroscopy uses a microphone and a piezoelectric element made of lead zirconate titanate (PZT) ceramics, or the like, to detect acoustic waves (see, for example, Jpn. Pat. Appln. KOKAI Publication Nos. 10-189 and 11-235331).
In addition to hemoglobin and glucose, photoacoustic spectroscopy can be used to determine other analytes in human tissue such as cholesterol, natural fat, bilirubin, collagen, and the like. Diagnosis of cutaneous cancer or breast cancer based on the results of the photoacoustic spectroscopy has recently proven its clinical usefulness. The photoacoustic spectroscopy utilizes a suitable substance selected from these substances and light having a wavelength at the substance selected exhibits highest absorption. Further it is increasingly expected that a diagnosis method be invented, which provides a two-dimensional image representing the concentration distribution of these substances.
While photoacoustic spectroscopy is used to measure substance concentration in tissue, ultrasound images have been extensively used for determination of the presence of morphological features, such as cysts and lumps, in human organs. Combining the distribution of substances and the morphological features in human tissue leads to better diagnosis and improved healthcare as it provides better characterization of the tissue, more accurate diagnosis for malignancies, and better definition of regions of abnormal pathology to guide in surgical removal of these regions.
Breast cancer is a major source of mortality in females. Screening for and early diagnosis of breast cancer are of tremendous value in cutting mortality rate and in health care cost containment. Current methods involve manual examination of breast tissue for unusual lumps and routine mammography to look for suspicious lesions. If a mammogram is deemed suspicious, it is followed by ultrasound imaging, and surgical biopsy. These set of steps take considerable time before reaching a final conclusion.
Non-invasive optical techniques offer the opportunity for determining blood vessel distribution in tissue, thus locating a potential tumor by the presence of abnormal vascularization in a tissue region.
Non-invasive optical techniques include time resolved light propagation in tissue. Another method is the measurement of the change in modulation and phase angle as photon density wave propagate in the tissue. These are presented is several journal articles (B. Chance “Near-infrared images using continuous, phase-modulated, and pulsed light with quantitation of blood and blood oxygenation” in Advances in Optical Biopsy and Optical Mammography, R. Alfano ed, Annals of the New York Academy of Sciences 1998; Volume 838: pages 29-45; by S. Fantini et al “Frequency domain optical mammography: Edge effect corrections” Medical Physics 1996; Volume 23: pages 1-6, and by M. A. Franceschini et al “Frequency Domain techniques enhance optical mammography; initial clinical results” Proceedings of the National Academy of Sciences USA 1997; Volume 94: pages 6468-6473 (1997)). These methods suffer from imprecision of image conversion and image distortions close to the edges of the body part, such as the breast.
Conventional imaging methods that include ultrasound, CAT scan, X-ray and MRI describe the morphology of the body part, in this case the breast without indicating the distribution of hemoglobin. Further, MRI and CAT scan require large expensive equipment that cannot be transformed easily.
A diagnostic method and apparatus that utilizes the morphological image and the distribution of substances in the morphological feature leads to better diagnosis.
Use of photoacoustic imaging to determine analyte distribution in breast tissue was described by A. A. Oraevsky et al “Laser opto-acoustic imaging of breast: Detection of cancer angiogenesis” SPIE Proceedings 1999; Volume 3597, pages: 352-363; and A. A. Oraevsky et al “Opto-acoustic imaging of blood for visualization and diagnostics of breast cancer” SPIE Proceedings 2002; Volume 4618, pages: 81-94. It is also described in U.S. Pat. No. 5,840,023 “Optoacoustic imaging for medical diagnosis”, EP 01/10295 “Photoacoustic monitoring of blood oxygenation”, and U.S. Pat. No. 6,309,352 B1 “Real Time optoacoustic monitoring of changes in tissue properties”.
Oraevsky et al use photoacoustic imaging alone without combination with ultrasound imaging. They do not teach combination of photoacoustic and ultrasound images that are detected using positioned ultrasound transducers. The method leads to the possibility of distortion of the vascular image due to effect of the morphological features on tissue bulk modulus.
Other application of optical methods to generate an image of analyte distribution in tissue is described by Q. Zhu et al in “Combined ultrasound and optical tomography imaging” SPIE Proceedings 1999; Volume 3579, pages: 364-370; and Q. Zhu et al “Optical imaging as an adjunct to ultrasound in differentiating benign from malignant lesions” SPIE Proceedings 1999; Volume 3579: pages 532-539. Zhu et al uses ultrasound imaging to define the morphological features in tissue and then apply frequency domain imaging to determine vascularization, e.g., hemoglobin distribution. Optical fibers and photomultiplier tubes are used as detectors for the optical method and ultrasound transducers are used for ultrasound imaging with less optimum positioning between the vascularization and the morphological images. Zhu et al, however, do not teach combination of photoacoustic and ultrasound images that are detected using positioned ultrasound transducers.
Research has been conducted on imaging methods using the photoacoustic effect for diagnosing breast cancer (see, for example, Alexander A et al., “Laser optoacoustic imaging of breast cancer in vivo”, Pros. SPIE, Vol. 4256, pp. 6-15, 2001). FIG. 19 illustrates a system 100 for acquiring photoacoustic image data, described in this reference. The system 100 is comprised of a laser generator 101, an optical fiber 103, an array of electroacoustic transducer elements 104 each having a concave surface, and a computer system 105. The laser generator 101 generates light pulses. The optical fiber 103 guides the light pulse to a breast 102 of a subject to be examined. The electroacoustic transducer elements 104 are placed facing the optical fiber 103. The computer system 105 controls transmission of optical pulses, acquires acoustic waves, and reconstructs an image. After the breast 102 is positioned between the optical fiber 103 and the array of electroacoustic transducer elements 104, the internal tissues in the breast 102 are irradiated with light (laser beam) from the optical fiber 103. The blood components in the internal tissues generate acoustic waves. The electroacoustic transducer elements 104 receive the acoustic waves.
In this method, the concentration of hemoglobin in blood, for example, can be measured with higher sensitivity than the concentration of any other substance components, by virtue of the photoacoustic effect based on a predetermined wavelength. Therefore, a photoacoustic image obtained from a tumor tissue such as a breast cancer in which the blood flow rate is higher than that in normal tissues can have higher detectability than an image obtained by an ultrasonic diagnosis apparatus, X-ray apparatus, MRI apparatus, or the like, which has conventionally been used. This is because vascularization, which is the number of blood vessels, and the blood flow rate are higher in the tumor tissue than in normal tissues, in order to accommodate the higher metabolic activity in the tumor. Increased vascularization occurs through generation of more blood vessels in the tumor and its surroundings. Generation of new blood vessels in tumors is known as angiogenesis.
The methods disclosed in the above references are designed to measure the concentration of a specific substance in a local region. However, none of these references teaches techniques of imaging concentration distributions.
The method described in above reference lacks operability. This is because, the optical fiber 103 and the array of electroacoustic transducer elements 104 opposite to each other, with the breast 102 being held between them. It is desirable to integrate the optical fiber 103 and the array of electroacoustic transducer elements 104, because air must be expelled, as much as possible, from the gap between the array and the subject, particularly when an image is reconstructed from the acoustic waves received from inside the subject.
In addition, image reconstruction using such acoustic waves (referred to as “photoacoustic imaging method” hereinafter) is performed only for a particular component such as hemoglobin. Hence, no signals can be obtained from any region that contains no such specific component. Therefore, when the photoacoustic imaging method is performed to examine the breast for cancer as described in non-patent reference 1, it is difficult to determine an accurate positional relationship between a tumor tissue and a healthy mammary gland tissue surrounding it.
There is therefore a need to develop a method and apparatus which diagnose disease states by combining imaging of morphological features and distribution of substance concentration within the features, while avoiding image distortion, incorporating a common body interface and common detector, for the imaging measurement and the substance distribution measurement. The method and the apparatus should lead to applying the same pressure, same air gaps, same interfaces to the imaging measurement and the substance distribution measurement.